System and method for determining spatial organization of atrial activation

ABSTRACT

A system and method evaluates the spatial organization of atrial activation sequences of a heart. Electrical activity of an atrium is sensed at a predetermined number of different localized locations within the atrium to generate a like predetermined number of electrograms. The electrogram generated for each localized location is cross-correlated with the electrograms generated for every other localized location to derive a set of correlation values. A space constant derivable from the correlation values or the correlation values themselves may be used to evaluate antiarrhythmic drug effectiveness or, within an implantable atrial defibrillator, atrial arrhythmia type.

BACKGROUND OF THE INVENTION

The present invention generally relates to a system and method fordetermining the extent of spatial organization of atrial activity of theheart. In accordance with additional aspects, the present invention maybe utilized to advantage in establishing atrial antiarrhythmic regimensincluding both appropriate drug screening and selection and chronicelectrical cardioverison strategies.

Atrial fibrillation is a common clinical problem, affecting more thanone million people in the United States alone, including up to tenpercent of those persons over the age of seventy-five. It is the leadingcause of cardiogenic embolism and, in the setting of hypertension and/ororganic heart disease, is associated with a four to six percent yearlyincidents of stroke.

Based upon insights of human studies and animal models, atrialfibrillation is believed to result from rapid and spatially disorganizedelectrical activity of the atria, with multiple activation waveletssweeping across the surface of the atria, resulting in an ever-changingpattern of electrical excitation. The absence of coordinated atrialactivation and regular, coordinated mechanical contraction, isresponsible for the clinical manifestations of atrial fibrillationincluding loss of hemodynamic efficiency, propensity forthromboembolism, and a rapid, irregular pulse rate.

The preferred clinical end-point for treatment of patients with atrialfibrillation is the restoration and maintenance of normal sinus rhythmwith its associated physiologic control of heart rate, preservation ofAV synchrony, and reduction of stroke risk. However, this strategy isoften frustrated by the inability to prospectively and objectivelyidentify effective antiarrhythmic regimens to prevent recurrences.Additionally, in recent years, the use of antiarrhythmic drugs foratrial fibrillation has been further complicated and attenuated byconcerns of potentially life-threatening proarrhythmia associated withempiric drug therapy.

Theoretical consideration, together with results from animal models ofatrial fibrillation have suggested that the susceptibility of the atrialelectrophysiologic substrate to atrial fibrillation may lend itself toobjective, quantitative description. In particular, it has been shown inthe dog model that atrial tissue wavelength, λ, (equal to the product ofconduction velocity and tissue refractory) plays a critical role inestablishing the susceptibility of the atria to atrial fibrillation,with short λ predisposing the atrial fibrillation and long λ makingatrial fibrillation nonsustainable.

While measurement of λ and drug-induced alterations in λ may provide anobjective strategy for the initial selection of antiarrhythmic agentsand subsequent measurement of drug effectiveness, its application in theclinical setting is unfortunately impractical. Its practicality islimited due to the inherent technical difficulties associated with thesimultaneous measurement of refractoriness and conduction velocity inthe intact human heart.

The present invention provides an objective measurement of the spatialorganization of atrial fibrillation to provide an objective assessmentof the electrophysiologic substrate and its susceptibility toarrhythmia. This is based upon the proposition that the extent ofspatial organization of activation during atrial fibrillation iscritically dependent upon the atrial tissue wavelength, λ. In accordancewith the present invention, the measurement of the spatial organizationof atrial fibrillation may be conveniently performed within the clinicalsetting thus making the procedure advantageous for the provision of anobjective strategy for the initial selection of anti-arrhythmia agentsand subsequent measurement of drug action in vivo. In addition, thedetermination of the spatial organization of atrial activity, inaccordance the present invention, may further be used to advantage inderiving strategies for the electrical cardioversion of atrialarrhythmias with an implantable atrial defibrillator.

SUMMARY OF THE INVENTION

The invention therefore provides a method of evaluating the spatialorganization of atrial activation sequences of a heart. The methodincludes the steps of sensing electrical activity of an atrium of aheart at a predetermined number of different localized locations withinthe atrium, wherein the localized locations are spaced apart bypreselected distances with respect to each other, generating a likepredetermined number of electrograms, each electrogram representing theelectrical activity sensed at each of the predetermined number oflocalized locations, and cross-correlating the electrogram generated foreach localized location with the electrogram generated for every otherlocalized location to derive a correlation value for each preselecteddistance.

The method may further include the steps of deriving an averagecorrelation value for each preselected distance and thereafter, derivinga space constant from the average correlation values.

The invention further provides a method of evaluating the effectivenessof a medication upon an atrial arrhythmia of a heart of a patient. Themethod includes the steps of sensing electrical activity of an atrium ofa heart at a predetermined number of different localized location withinthe atrium, wherein the localized locations are spaced apart bypreselected distances with respect to each other, generating a likepredetermined number of electrograms, each electrogram representing theelectrical activity sensed at each of the predetermined number oflocalized locations, and cross-correlating the electrogram generated forat least one of the localized locations with the electrogram generatedfor at least one other one of the localized locations to derive apre-medication correlation value for at least one of the preselecteddistances. The method further includes the steps of administering themedication to the patient, after a predetermined period of timerepeating the first and second above recited method steps, thereaftercross-correlating the electrogram generated for the at least one of thelocalized locations with the electrogram generated for the at leastother of the localized location to derive a post-medication correlationvalue for the at least one of the preselected distances, and comparingthe pre-medication correlation value to the post-medication correlationvalue.

The present invention still further provides a method of discriminatingbetween normal sinus rhythm and atrial arrhythmias of a heart. Themethod includes the steps of sensing electrical activity of an atrium ofthe heart at at least first and second different localized locationswithin the atrium, wherein the first and second localized locations arespaced apart by a preselected distance, generating first and secondelectrograms representing the electrical activity sensed that the firstand second localized locations respectively, cross-correlating the firstand second electrograms to derive a correlation value, and comparing thecorrelation value to a predetermined standard.

The present invention still further provides a system for discriminatingbetween normal sinus rhythm and an atrial arrhythmia of atria of aheart. The system includes sensing means for sensing electrical activityof an atrium of the heart at at least first and second differentlocalized locations within the atrium, the first and second localizedlocations being spaced apart by a preselected distance, means forgenerating first and second electrograms representing the electricalactivity sensed by the sensing means at the first and second localizedlocations respectively, means for cross-correlating the first and secondelectrograms to derive a correlation value, and means for comparing thecorrelation value to a predetermined standard.

The present invention still further provides an atrialcardiovertor/defibrillator comprising criteria establishing means forproviding a respective different criteria for each of different types ofatrial arrhythmia, therapy means for providing a corresponding therapyto the heart for each of the different types of atrial arrhythmia, andclassifying means for identifying one of the types of atrial arrhythmiaand causing the therapy means to provide the therapy to the heartcorresponding to the identified one of the types of atrial arrhythmia.The classifying means includes sensing means for sensing electricalactivity of an atrium of the heart at at least first and seconddifferent localized locations within the atrium, the first and secondlocalized locations being spaced apart by a preselected distance, meansfor generating first and second electrograms representing the electricalactivity sensed by the sensing means at the first and second localizedlocations respectively, means for cross-correlating the first and secondelectrograms to derive a correlation value, and means for comparing thecorrelation value to the different criteria.

BRIEF DESCRIPTION OF THE DRAWINGS

The features of the present invention which are believed to be novel areset forth with particularity in the appended claims. The invention,together with further objects and advantage thereof, may be bestunderstood by making reference to the following description taken inconjunction with the accompanying drawing, in several figures of whichlike referenced numerals identify identical elements, and wherein:

FIG. 1 is a schematic block diagram of a system for evaluating thespatial organization of atrial activity of the atria of a heart inaccordance with the present invention;

FIG. 2 is a graph plotting correlation values derived in accordance withthe present invention versus sensing location spacing for normal sinusrhythm, atrial flutter, and atrial fibrillation;

FIG. 3 is a graph plotting correlation values derived in accordance withthe present invention versus sensing location spacing for pre-medicationatrial activity and post-medication atrial activity to illustrate themanner in which the present invention may be utilized to advantage inthe screening of antiarrhythmic drugs;

FIG. 4 is a schematic block diagram of an implantable atrialdefibrillator embodying the present invention shown in association witha human heart in need of atrial arrhythmia monitoring, atrial arrhythmiaclassifying, and potential atrial cardioverting.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Referring now to FIG. 1, it illustrates a human heart 10 and a system 20for evaluating the spatial organization of atrial activation sequencesof the atria 12 and 14 of the heart 10 in accordance with the presentinvention. The system 20 generally includes a temporary catheter 22, aplurality of sense amplifiers 24, a like plurality of band-pass filters26, a multiplexor 28, and an analog to digital converter 30. The systemfurther includes a random access memory 32, a microprocessor 34, and aprinter 36.

The catheter 22 is preferably a decapolar catheter with five electrodepairs 38, 40, 42, 44, and 46. Each electrode is preferably two (2)millimeter in width and the electrodes of each pair are preferablyspaced apart by two (2) millimeter. This enables localized sensing ofatrial activity at each of the electrode pairs 38, 40, 42, 44, and 46.The electrode pairs preferably are spaced on eleven (11) millimetercenters. The catheter 22 is fed as illustrated down the superior venacava 16 and into the right atrium 12 for sensing atrial activity of theheart 10 at five different localized locations within the right atrium12. The localized locations are spaced apart within the atrium 12 bycombinations of eleven (11) millimeter, twenty-two (22) millimeter,thirty-three (33) millimeter, and forty-four (44) millimeter.

The plurality of sense amplifiers 26 include five sense amplifiers 48,50, 52, 54, and 56 having input pairs coupled to the electrode pairs 38,40, 42, 44, and 46 respectively. Each of the sense amplifiers 48, 50,52, 54, and 56 generates an electrogram at its output representing theelectrical activity sensed by its corresponding respective electrodepair 38, 40, 42, 44, and 46.

The plurality of band-pass filters includes band-pass filters 58, 60,62, 64, and 66. Each band-pass filter preferably has a band-pass of0.5-400 Hz and has an input coupled to the output of a respective givenone of the sense amplifiers 48, 50, 52, 54, and 56. As a result, aband-pass filtered electrogram representing the atrial activity sensedat each of the electrode pairs 38, 40, 42, 44, and 46 is developed ateach respective output of the band-pass filters 58, 60, 62, 64, and 66.

The band-pass filtered electrograms are then repeatedly and sequentiallyapplied to the analog to digital converter 30 by the multiplexor 28. Theanalog to digital converter 30 digitizes the electrograms which are thendirectly stored in the random access memory 32 for off-line processingby microprocessor 34 as will be described hereinafter. Preferably, theelectrograms are sensed, digitized, and stored in the random accessmemory 32 during a continuous sixty (60) second period to provide asufficient number of atrial activations upon which to base the spatialorganization analysis. The electrogram data stored in the random accessmemory 32 will be representative of the electrograms sensed by eachelectrode pair over the sixty (60) second time period.

The microprocessor 34 performs off-line processing and generatesanalytical results. To that end, the microprocessor executesinstructions stored in the random access memory 32 or other memory (notshown) for operating on the electrogram data stored in the random accessmemory 32. To that end, the instructions define a plurality ofoperational stages including an electrogram conditioning stage 70, across-correlation stage 72, an averaging stage 74, a space constantstage 76, and a compare stage 80.

The electrogram data is first operated upon by the electrogramconditioning stage 70. The electrogram conditioning stage 70 performsdigital processing on the electrograms so as to generate a likepredetermined number of electrograms with each electrogram representingthe sequence of activations sensed at each of the predetermined numberof localized locations.

To that end, the operating instructions defining this stage preferablycause the microprocessor to first parse the electrograms intonon-overlapping segments of two (2) to ten (10) seconds to maintain,regardless of atrial rhythm, ten (10) to twelve (12) activations in eachanalysis segment. The data segments are then band-passed filtered usinga digital, zero-phase, third order Butterworth filter algorithm withcutoffs of 40-250 Hz. The absolute value of the resulting output of eachelectrogram is then low-pass filtered using a similar third orderButterworth filter algorithm with a 20 Hz cut-off. This process extractsa time-varying waveform proportional to the amplitude of thehigh-frequency components (40-250 Hz) in each of the original fiveelectrograms. Each resultant waveform is then normalized to contain unitenergy.

The cross-correlation stage 72 then calculates the cross-correlationfunction between all possible paired combinations of the fiveelectrograms. This results in ten total correlations at four fixeddistances being calculated. The cross-correlation of the electrograms ispreferably carried out with a standard cross-correlation function. Foreach data segment, the absolute peak of the cross-correlation functionis preferably taken to represent the extent to which activationsequences were correlated for that period of time. The foregoingoperation is repeated by the cross-correlation stage 72 on sequentialdata segments for the entire sixty (60) seconds of stored data for eachof the five electrograms. This allows construction of a correlationversus time relationship from which the average correlation over theentire data record can be determined.

The foregoing cross-correlation process derives ten differentcorrelation values, four values for eleven (11) millimeter electrodepair separation, three correlation values for twenty-two (22) millimeterelectrode pair separation, two correlation values for thirty-three (33)millimeter electrode pair separation, and only one correlation value fora forty-four (44) millimeter electrode pair separation.

After the correlation values are determined, the values for each givenseparate distance are averaged by the average correlation value stage 74to provide a single correlation value for each electrode pair spacingwhich may be printed out on the printer 36.

FIG. 2 is a graph, plotting correlation value versus distance obtainedas described above for the same patient during normal sinus rhythm,atrial flutter, and atrial fibrillation. It can be noted that duringnormal sinus rhythm, the correlation value for all electrode pairspacing is essentially unity and only slightly less during atrialflutter. This indicates that during normal sinus rhythm and atrialflutter, there is a high degree of spatial organization. However, duringatrial fibrillation, it will be noted that the correlation value issubstantially less than unity for all electrode pair spacing. Hence,during atrial fibrillation, there is a comparatively low degree ofspatial organization. These differences in correlation values, as willbe seen hereinafter, may be utilized to advantage in discriminatingbetween normal sinus rhythm and atrial arrhythmias.

Additional information may be further derived from the graph of FIG. 2,namely the space constant (δ) which is a proportional measure of thepreviously referred to atrial tissue wavelength (λ). The reason thespace constant may be considered an estimate of the atrial tissuewavelength is because the relation between the spatial organization ofactivation during atrial fibrillation and the atrial tissue wavelengthis a natural consequence of the wavelet hypothesis of atrialfibrillation. At any point in time for each wavelet on the surface ofthe atria, there is a region of tissue under the direct influence ofthat wavelet (i.e., that wavelet's domain). Within the wavelet's domain,activations are well correlated, having been initiated by this onewavelet. The area of that domain varies over time and space, but at anyinstant, within the domain there must be a self-avoiding path (the wakeof the wavelet) with a link equal to or greater than the atrial tissuewavelength. In the limit of leading circle reentry, the minimum area forthe domain of a wavelet would then be the area of the circle withcircumference equal to the atrial tissue wavelength. Hence, atrialactivation sequences within a small region are well correlated whileactivation sequences beyond some distance are no longer well correlated(reflective of their participation in different wavelets). The spaceconstant (the distance over which activation sequences are wellcorrelated) can then serve as an objective measure for a spatialorganization of electrical activation during atrial fibrillation as wellas an estimator of atrial tissue wavelength.

To derive the space constant during atrial fibrillation, the correlationvalues versus distance graph of FIG. 2 for atrial fibrillation may beapproximated by the space constant stage 76 as a decaying exponentialfunction of, CC(d)=e^(-d/)δ where CC(d) is the cross-correlation valueas a function of distance, d is the electrode pair spacing, and δ is thespace constant. The space constant, δ, may be determined by the spaceconstant stage 16 by determining the statistical best fit δ for eachdata set by finding the value of δ which minimizes the weightedmean-squared error between the exponential function and the data wherethe waiting function for each value of cross-correlation is equal to thenumber of observations available at that point. Thus, the measure ofcorrelation for eleven (11) millimeter electrode pair spacing is theaverage of four measures, with error at the point weighted by four,while that for forty-four (44) millimeter electrode pair spacing is asingle measure, with the error at that point receiving unity weighted.

The value of δ determined in this fashion serves as a single objectiveand quantitative measure of the extent of spatial organization ofactivation sequences during atrial arrhythmias in general, and duringatrial fibrillation in particular. As will be noted from FIG. 2, duringnormal sinus rhythm and atrial flutter, the space constant is infinitelylarge with respect to the size of the atria. However, during atrialfibrillation, the space constant is monotonically decreasing withincreasing electrode pair spacing. The difference in the space constantmay be utilized to advantage in discriminating between normal sinusrhythm and atrial arrhythmias.

Referring now to FIG. 3, it is a graph of correlation values versuselectrode pair separation to illustrate the utility of the presentinvention in the screening of antiarrhythmic drugs. A first plot 82displays the correction values from electrograms obtained during atrialfibrillation and before administration of the antiarrhythmic drugProcainamide (PCA) to the patient. Plots 84 and 86 display thecorrelation values from electrograms obtained during atrial fibrillationat five (5) and ten (10) minute intervals respectively after PCA wasadministered. All correlation values illustrated in FIG. 3 were derivedin the manner as previously described in connection with the discussionof FIG. 1.

As will be noted in FIG. 3, after PCA was administered, there was aprominent increase in the correlation values for all electrode pairseparations. Since the correlation values increased with time, thespatial organization of the atria increased and the medication, giventhese results, was known to be effective for this patient. It alsonaturally follows that the space constant was increased and may becalculated from the correlation values of plots 82, 84 and 86 in amanner as previously described. Deriving the space constants has theincreased reliability of simultaneously taking into account all of thecorrelation values generated for each plot. However, the results of FIG.3 demonstrably show that any one electrode separation may be relied uponfor the screening process requiring just two electrode pairs at almostany known separation between, for example, ten (10) millimeter andforty-four (44) millimeter. In this way, only two pair of electrogramsneed be taken, one pair of electrograms prior to administration of themedication for the generation of a pre-medication correlation value andthe other pair of electrograms after administration of the medicationfor the generation of a post-medication correlation value. Thepost-medication correlation value can then be compared to thepre-medication correlation value by the compare stage 80 of themicroprocessor 34 (FIG. 1). The results may then be printed by theprinter 36 to indicate the effectiveness of the medication. Preferably,the results include the pre-medication and post-medication correlationvalues.

Referring now to FIG. 4, it illustrates an implantable automatic atrialdefibrillator 130 embodying the present invention. It is shownassociated with a heart 100 in need of atrial arrhythmia monitoring andpotential cardioversion.

The atrial defibrillator 130 includes an implantable enclosure 132 andan implantable lead system including an intravascular lead 134 and anendocardial lead 136. The endocardial lead 136 has tip and ringelectrodes 138 and 140 respectively adapted for placement in the rightventricle 112. The endocardial lead 136 further includes proximalelectrode pairs 142 and 144, each pair of electrodes for sensinglocalized activity to the right atria 116. The electrode pairs 142 and144 are preferably structured as previously described and separated byan interelectrode spacing of twenty-two (22) millimeter, for example.

The intravasuclar lead 134 has a tip electrode 146 adapted for placementin the coronary sinus 122 or the great cardiac vein 123 and a ringelectrode 148 adapted for placement in the superior vena cava 120 orright atrium 116. An alternate lead system may include separate leadsfor electrodes 146 and 148.

Electrode pairs 142 and 144 of lead 136 sense localized atrial activityof the heart. Electrodes 146 and 148 of lead 134 perform the function ofapplying cardioverting electrical energy across the right and left atria116 and 118 of the heart. Electrodes 138 and 140 sense localizedactivity of the right ventricle 112 to enable detection of R waves forsynchronizing the application of the cardioverting energy to the atriawith an R wave.

Within the enclosure 132, the atrial defibrillator 130 includes senseamplifiers 150 and 152, multiplexor 154, analog to digital converter156, and random access memory 158. Sense amplifier 150 is couple to theelectrode pair 142 and sense amplifier 152 is couple to the electrodepair 144. The sense amplifiers 150 and 152 generate electrogram signalsrepresenting the localized activity sensed by electrode pairs 142 and144 respectively to provide electrograms for cross-correlation afterelectrogram conditioning. The cross-correlation of the electrograms maybe performed as previously described to derive a correlation value. Thecorrelation value can then be compared to atrial arrhythmia criteriastored in a memory portion 160 of random access memory 158 to determineif the atria are in normal sinus rhythm, atrial flutter, or atrialfibrillation.

Another sense amplifier 162 is coupled to electrodes 138 and 140 of lead136. The sense amplifier 162 has an output coupled to an R wave detector164 of the type well known in the art for isolating R waves. The R wavedetection of the detector 164 enables the cardioverting electricalenergy to be applied to the atria in synchronism with an R wave of theright ventricle.

The outputs of the sense amplifiers 150 and 152 are coupled to theanalog to digital converter 156 through the multiplexor 154. The analogto digital converter 156 digitizes the electrograms provided by theamplifiers 150 and 152 to generate electrogram digital data samples.Electrogram samples are then conveyed to the random access memory 150.The sense amplifiers 150 and 152 each preferably includes a filter forprefiltering the atrial electrograms prior to multiplexing as previouslydescribed in connection with FIG. 1.

A microprocessor 166 implements an atrial arrhythmia detector anddiscriminator 168 responsive to the atrial electrogram digital samplestored in the random access memory 158. To that end, the microprocessor166 implements the electrogram conditioning 170 and thecross-correlation 172 in a manner as previously described. Hence, atrialactivity is sensed for a period of, for example, sixty (60) seconds, andthe electrograms representing the atrial activity for the sixty (60)second period are conditioned by the electrogram conditioning stage 170and then cross-correlated by the cross-correlation stage 172 aspreviously described to derive a correlation value.

The atrial arrhythmia criteria stored in memory portion 160 of randomaccess memory 158 may be representative of predetermined correlationvalues representing correlation value ranges representing normal sinusrhythm, atrial flutter, and atrial fibrillation. When thecross-correlation stage 172 derives the correlation value, themicroprocessor through a compare stage 174 compares the correlationvalue to the correlation value ranges stored in memory portion 160. Inthis manner, the microprocessor 166 determines whether the heart is innormal sinus rhythm, atrial flutter, or atrial fibrillation.

The cardioverting stage 180 provides a different cardioverting therapyfor each respective different type of atrial arrhythmia. Thecardioverting stage 180 includes a therapy control 182 and a charge anddelivery control 184 implemented by the microprocessor 166 and a chargerand storage capacitor circuit 184 and discharge circuit 186. The therapycontrol 182 responsive to the atrial arrhythmia type detected by thecomparator 174 selects a corresponding one of the available atrialtherapies. For example, for atrial fibrillation, the therapy may includea relatively high voltage cardioverting discharge to the atria while foratrial flutter, the therapy may include a relatively low voltagecardioverting discharge to the atria. Upon determining which therapy todeliver, the therapy control 182 controls the charge delivery control184 so that the storage capacitor of circuit 184 is charged to a voltageappropriate for the atrial arrhythmia type. When the capacitor ofcircuit 184 is charged to the appropriate voltage, the discharge circuit186 discharges the voltage stored in the capacitor of circuit 184 insynchronise with an R wave detected by the R wave detector 164. Thedischarged voltage is applied across electrodes 146 and 148 of lead 134for cardioverting the atria.

While particular embodiments of the present invention have been shownand described, modifications may be made. For example, the system andmethod of the present invention may be used to advantage in implantableautomatic atrial defibrillators of the type which provide a respectiveand corresponding therapy for each of different types of atrialfibrillation. Such an implantable atrial defibrillator is disclosed, forexample, in co-pending application Ser. No. 08/331,898 filed Oct. 31,1994 for ATRIAL FIBRILLATION TYPE SELECTIVE CARDIOVERTOR AND METHOD.Hence, it is therefore intended to cover in the appended claims all suchchanges and modifications which fall within the true spirit and scope ofthe invention.

What is claimed is:
 1. A method of evaluating the effectiveness of a medication towards terminating an atrial arrhythmia of a heart of a patient, said method including the steps of:(a) sensing electrical activity of an atrium of a heart at a predetermined number of different localized locations within the atrium, the localized locations being spaced apart by preselected distances with respect to each other; (b) generating a like predetermined number of electrograms, each electrogram representing the electrical activity sensed at each of the predetermined number of localized locations; (c) cross-correlating the electrogram generated for at least one of the localized locations with the electrogram generated for at least one other one of the localized locations to derive a pre-medication correlation value for at least one of the preselected distances; (d) administering the medication to the patient; (e) after a predetermined period of time, repeating steps (a) and (b); (f) cross-correlating the electrogram generated for said at least one of the localized locations with the electrogram generated for said at least one other of the localized locations to derive a post-medication correlation value for said at least one of the preselected distances; (g) comparing the pre-medication correlation value to the post-medication correlation value, and (h) determining if post-medication correlation value is greater than the pre-medication correlation value.
 2. A method of evaluating the effectiveness of a medication upon an atrial arrhythmia of a heart of a patient, said method including the steps of:(a) sensing electrical activity of an atrium of a heart at a predetermined number of different localized locations within the atrium, the localized locations being spaced apart by preselected distances with respect to each other; (b) generating a like predetermined number of electrograms, each electrogram representing the electrical activity sensed at each of the predetermined number of localized locations; (c) cross-correlating the electrogram generated for each localized location with the electrogram generated for every other localized location to derive a pre-medication correlation value for each preselected distance; (d) administering the medication to the patient; (e) after a predetermined period of time, repeating steps (a) and (b); (f) cross-correlating the electrogram generated for each localized location with the electrogram generated for every other localized location to derive a post-medication correlation value for each preselected distance; (g) deriving a pre-medication average correlation value from the pre-medication correlation values for each preselected distance; (h) deriving a pre-medication space constant from the pre-medication average correlation values; (i) deriving a post-medication average correlation value from the post-medication correlation value for each preselected distance; (j) deriving a post-medication space constant from the post-medication average correlation values; (k) comparing the pre-medication space constant to the post-medication space constant; and (l) determining if the post-medication space constant is greater then the pre-medication space constant. 